Making choices regarding characterization of environmental exposures

1. Making choices regarding characterization of environmental exposures Environmental Exposure Assessment Workshop for Population Studies Banff, Alberta Feb. 2008 J.R. Brook Environment Canada University of Toronto

2. Environmental E E Exposure

3. The Challenge of Assessing Exposure Canadian Healthy Infant Longitudinal Development Which Exposures do we quantify and how?

4. Environmental exposures that have been associated with the development or exacerbation of childhood asthma

5. There has been decreases in the cost of obtaining detailed genetic information and advances in computational methods. BUT Exposure measurement remains expensive and more detail = more expensive Limitations due to ethical considerations Compromise is necessary

6. Advances in exposure characterization • Measurement technologies • Dust collection approaches • Chemical analysis of dust • Small passive and active samplers • Biomarkers • Greater coverage through satellite observations • Models • Empirical and physical outdoor air models • Indoor Infiltration models • Probabilistic exposure models • Greater integration • Questionnaires • More detail (different questions, behaviour) • Ongoing validation

7. Strategies for prioritizing the exposures of interest • Public Health Importance • exposures that are modifiable, are common across the population and are hypothesized (or shown) to be associated with the development of asthma • Measurement Capability • a validated method for characterizing the exposure is available and resources are available to collect the desired data

8. Biological Mechanisms • focus on an exposure that is hypothesized to act through the same biological pathway as an other exposures that has been associated with asthma • help develop biomarkers to quantify exposure and/or effect based upon features of the biological pathway • Potential for Data Pooling • measure the same exposures at the same time points using the same methods so that the resulting data can be combined with other studies • requires specific knowledge of the other studies and flexibility in the design of the new study • larger sample size • potential for greater variability in exposure

9. Factors Controlling Power inGene X Environment Studies • exposure prevalence • study populations with large exposure prevalence and contrasts • measurement error • can be directly influenced by study design • reducing error is an efficient way to improve power • true effect size • study environmental factors or genetic effects that are hypothesized to be large based on animal (or microarray) studies • genotype (phenotype) prevalence • study populations with large prevalence Wong et al. 2003, IJE

10. Reducing Measurement Error • well-defined research questions • more repeat measurements of exposure • better timing of exposure measurements • use of less expensive exposure surrogates that are better correlated with the specific outcome of interest • more accurate/specific genotyping, consistent phenotyping • improved understanding of the mechanism of effect (epigenetics) • Helps target the desired exposure

11. Technological Advances

12. Integrating Sources of Exposure Info.Measurements + Model + Questionnaires = MODEL Measurements Questionnaires LUR – Land-Use Regression Long term time-integrated exposures But at specific time points (?)

13. Annual Average NO2 Observed from Space

14. Toronto

15. Best Resolution of Current AQ Models

16. Satellite observations Hi-res Emissions Measurement networks Air Quality Model ‘Fused’ spatio-temporal concentration/exposure Empirical models

17. Issues to consider when applying LUR to studies of air pollution and health • differential exposures at home, outdoors and in the workplace • subject mobility • the relevant time period exposure (and duration of relevant exposure) • exposures to multiple pollutants • tracking effect modifiers • variability in infiltration indoors

18. Is there a more-direct measure? Air exchange rate adjusted R2=0.43 N N detached garage Att. w/door Adj.-NO2 Outside Home (ppb) Vehicle exhaust tracer in dust (mg/kg) R2=0.01 NO2 Outside Home (ppb)

19. Standard biological indicators of allergens • Isolate community DNA for new scans • Chemical Indicators ofmotor vehicle exhaust and phthalate exposures

20. Combining Existing CohortsCompromises, compromises Highest common denominator • Outdoor air exposure can often be reconstructed • Residence at recruitment • Residence during pregnancy and in early life • Complete residence history • Proximity to source(s) • Dispersion models • More validation is desired • Questionnaires • How specific, how validated, how often ? • Geographic/cultural differences in their meaning • Evaluation of similarities/differences is desired

21. How do we optimize our environmental exposure characterization?(for G x E research) • Many options • Just need time and money • Efficiency • Comes from asking the right question(s)

22. PARSIFAL Schram-Bijkerk et al. 2006 INDOOR AIR

23. Exposure information that can be collected from questionnaires

24. Exposure information that can be collected from questionnaires

25. Nitrogen Dioxide vs. Traffic pollution 1000 NO2 (r=0.67 ) 800 600 Hopanes (pg m-3) 400 200 0 10 20 30 40 50 60 NO2 (ppb)